A pandemic (from Greek πᾶν, pan, "all" and δῆμος, demos, "people") is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of people. A widespread endemic disease with a stable number of infected people is not a pandemic. Widespread endemic diseases with a stable number of infected people such as recurrences of seasonal influenza are generally excluded as they occur simultaneously in large regions of the globe rather than being spread worldwide.

Throughout human history, there have been a number of pandemics of diseases such as smallpox and tuberculosis. The most fatal pandemic in recorded history was the Black Death (also known as The Plague), which killed an estimated 75–200 million people in the 14th century. Other notable pandemics include the 1918 influenza pandemic (Spanish flu). Current pandemics include COVID-19 and HIV/AIDS.

resulted in dramatic mortality worldwide]]
A pandemic (from Greek πᾶν pan “all” + δῆμος demos “people”) is an epidemic of infectious disease that has spread through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic. Further, flu pandemics generally exclude recurrences of seasonal flu. Throughout history there have been a number of pandemics, such as smallpox and tuberculosis. More recent pandemics include the HIV pandemic as well as the 1918 and 2009H1N1 pandemics.

Definition and stages

A pandemic is an epidemic occurring on a scale which crosses international boundaries, usually affecting a large number of people.<ref name=Porta2008>

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The World Health Organization (WHO) has a six-stage classification that describes the process by which a novel influenza virus moves from the first few infections in humans through to a pandemic. This starts with the virus mostly infecting animals, with a few cases where animals infect people, then moves through the stage where the virus begins to spread directly between people, and ends with a pandemic when infections from the new virus have spread worldwide.<ref>Current WHO phase of pandemic alertWorld Health Organization 2009</ref>

A disease or condition is not a pandemic merely because it is widespread or kills many people; it must also be infectious. For instance, cancer is responsible for many deaths but is not considered a pandemic because the disease is not infectious or contagious.

In a virtual press conference in May 2009 on the influenza pandemic, Dr Keiji Fukuda, Assistant Director-General ad Interim for Health Security and Environment, WHO said “An easy way to think about pandemic … is to say: a pandemic is a global outbreak. Then you might ask yourself: “What is a global outbreak”? Global outbreak means that we see both spread of the agent … and then we see disease activities in addition to the spread of the virus.”<ref>

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In planning for a possible influenza pandemic, the WHO published a document on pandemic preparedness guidance in 1999, revised in 2005 and in February 2009, defining phases and appropriate actions for each phase in an aide memoir entitled WHO pandemic phase descriptions and main actions by phase. The 2009 revision, including definitions of a pandemic and the phases leading to its declaration, were finalized in February 2009. The pandemic H1N1 2009 virus, was neither on the horizon at that time nor mentioned in the document <ref>

</ref> All versions of this document refer to influenza. The phases are defined by the spread of the disease; virulence and mortality are not mentioned in the current WHO definition, although these factors have previously been included.<ref>

</ref> Effective education about safer sexual practices and bloodborne infection precautions training have helped to slow down infection rates in several African countries sponsoring national education programs. Infection rates are rising again in Asia and the Americas. AIDS could kill 31 million people in India and 18 million in China by 2025, according to projections by U.N. population researchers.<ref>AIDS Toll May Reach 100 Million in Africa. Washington Post. June 4, 2006.</ref> AIDS death toll in Africa may reach 90–100 million by 2025.<ref>

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Pandemics and notable epidemics through history

There have been a number of significant pandemics recorded in human history, generally zoonoses which came about with domestication of animals, such as influenza and tuberculosis. There have been a number of particularly significant epidemics that deserve mention above the “mere” destruction of cities:

Plague of Athens, 430 BC. Typhoid fever killed a quarter of the Athenian troops, and a quarter of the population over four years. This disease fatally weakened the dominance of Athens, but the sheer virulence of the disease prevented its wider spread; i.e. it killed off its hosts at a rate faster than they could spread it. The exact cause of the plague was unknown for many years. In January 2006, researchers from the University of Athens analyzed teeth recovered from a mass grave underneath the city, and confirmed the presence of bacteria responsible for typhoid.<ref>"Ancient Athenian Plague Proves to Be Typhoid". Scientific American. January 25, 2006.</ref>

in Martigues, France]]

Antonine Plague, 165–180. Possibly smallpox brought to the Italian peninsula by soldiers returning from the Near East; it killed a quarter of those infected, and up to five million in all.<ref>Past pandemics that ravaged Europe. BBC News, November 7. 2005</ref> At the height of a second outbreak, the Plague of Cyprian (251–266), which may have been the same disease, 5,000 people a day were said to be dying in Rome.

Plague of Justinian, from 541 to 750, was the first recorded outbreak of the bubonic plague. It started in Egypt, and reached Constantinople the following spring, killing (according to the Byzantine chronicler Procopius) 10,000 a day at its height, and perhaps 40% of the city's inhabitants. The plague went on to eliminate a quarter to a half of the human population that it struck throughout the known world.<ref>

Black Death, started 14th century. The total number of deaths worldwide is estimated at 75 million people.<ref>New MOL Archaeology monograph: Black Death cemetery. Archaeology at the Museum of London.</ref> Eight hundred years after the last outbreak, the plague returned to Europe. Starting in Asia, the disease reached Mediterranean and western Europe in 1348 (possibly from Italian merchants fleeing fighting in Crimea), and killed an estimated 20 to 30 million Europeans in six years;<ref>Death on a Grand Scale. MedHunters.</ref> a third of the total population,<ref>Stéphane Barry and Norbert Gualde, in L'Histoire n° 310, June 2006, pp.45–46, say “between one-third and two-thirds”; Robert Gottfried (1983). “Black Death” in Dictionary of the Middle Ages, volume 2, pp.257–67, says “between 25 and 45&nbsp;percent”.</ref> and up to a half in the worst-affected urban areas.<ref>Plague – LoveToKnow 1911. 1911encyclopedia.org.</ref> It was the first of a cycle of European plague epidemics that continued until the 18th century.<ref>

</ref> During this period, more than 100 plague epidemics swept across Europe.<ref>

</ref> In England, for example, epidemics would continue in two to five-year cycles from 1361 to 1480.<ref>

(compiled 1540–1585)]]
Encounters between European explorers and populations in the rest of the world often introduced local epidemics of extraordinary virulence. Disease killed part of the native population of the Canary Islands in the 16th century (Guanches). Half the native population of Hispaniola in 1518 was killed by smallpox. Smallpox also ravaged Mexico in the 1520s, killing 150,000 in Tenochtitlán alone, including the emperor, and Peru in the 1530s, aiding the European conquerors.<ref>

</ref> From the beginning of the 20th century onwards, the elimination or control of disease in tropical countries became a driving force for all colonial powers.<ref>Conquest and Disease or Colonialism and Health?, Gresham College | Lectures and Events</ref> The sleeping sickness epidemic in Africa was arrested due to mobile teams systematically screening millions of people at risk.<ref>

Cholera

From a local disease, cholera became one of the most widespread and deadly diseases of the 19th century, killing tens of millions of people.<ref>.Kelley Lee (2003) “Health impacts of globalization: towards global governance”. Palgrave Macmillan. p.131. ISBN 0-333-80254-3</ref>

</ref> It extended as far as China, Indonesia (where more than 100,000 people succumbed on the island of Java alone) and the Caspian Sea before receding. Deaths in India between 1817 and 1860 are estimated to have exceeded 15 million persons. Another 23 million died between 1865 and 1917. Russian deaths during a similar period exceeded 2 million.<ref>

Third pandemic 1852–1860. Mainly affected Russia, with over a million deaths. In 1852, cholera spread east to Indonesia and later invaded China and Japan in 1854. The Philippines were infected in 1858 and Korea in 1859. In 1859, an outbreak in Bengal again led to the transmission of the disease to Iran, Iraq, Arabia and Russia.<ref>Asiatic Cholera Pandemic of 1846–63 . UCLA School of Public Health.</ref> Throughout Spain, cholera caused more than 236,000 deaths in 1854–55.<ref>

The first influenza pandemic was recorded in 1580 and since then influenza pandemics occurred every 10 to 30 years.<ref>"Pandemic Flu". Department of Health and Social Security.</ref><ref>Beveridge, W.I.B. (1977) Influenza: The Last Great Plague: An Unfinished Story of Discovery, New York: Prodist. ISBN 0-88202-118-4.</ref><ref>

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The 1889–1890 flu pandemic, also known as Russian Flu, was first reported in May 1889 in Bukhara, Uzbekistan. By October, it had reached Tomsk and the Caucasus. It rapidly spread west and hit North America in December 1889, South America in February–April 1890, India in February–March 1890, and Australia in March–April 1890. The H3N8 and H2N2 subtypes of the Influenza A virus have each been identified as possible causes. It had a very high attack and mortality rate. About 1 million people died in this pandemic.“<ref>CIDRAP article Pandemic Influenza Last updated 16 June 2011</ref>

The ”Spanish flu“, 1918–1919. First identified early in March 1918 in US troops training at Camp Funston, Kansas. By October 1918, it had spread to become a worldwide pandemic on all continents, and eventually infected about one-third of the world's population (or ≈500 million persons).<ref name=“Taubenberger”/> Unusually deadly and virulent, it ended nearly as quickly as it began, vanishing completely within 18 months. In six months, some 50 million were dead;<ref name = “Taubenberger”>

The ”Asian Flu“, 1957–58. An H2N2 virus caused about 70,000 deaths in the United States. First identified in China in late February 1957, the Asian flu spread to the United States by June 1957. It caused about 2 million deaths globally.<ref>Q&A: Swine flu. BBC News. April 27, 2009.</ref>

The ”Hong Kong Flu“, 1968–69. An H3N2 caused about 34,000 deaths in the United States. This virus was first detected in Hong Kong in early 1968, and spread to the United States later that year. This pandemic of 1968 and 1969 killed approximately one million people worldwide.<ref>

Typhus

Typhus is sometimes called “camp fever” because of its pattern of flaring up in times of strife. (It is also known as “gaol fever” and “ship fever”, for its habits of spreading wildly in cramped quarters, such as jails and ships.) Emerging during the Crusades, it had its first impact in Europe in 1489, in Spain. During fighting between the Christian Spaniards and the Muslims in Granada, the Spanish lost 3,000 to war casualties, and 20,000 to typhus. In 1528, the French lost 18,000 troops in Italy, and lost supremacy in Italy to the Spanish. In 1542, 30,000 soldiers died of typhus while fighting the Ottomans in the Balkans.

During the Thirty Years' War (1618–1648), about 8 million Germans were killed by bubonic plague and typhus.<ref>War and Pestilence. TIME. April 29, 1940</ref> The disease also played a major role in the destruction of Napoleon's Grande Armée in Russia in 1812. Felix Markham thinks that 450,000 soldiers crossed the Neman on 25 June 1812, of whom less than 40,000 recrossed in anything like a recognizable military formation.<ref>See a large copy of the chart here: http://www.adept-plm.com/Newsletter/NapoleonsMarch.htm, but discussed at length in Edward Tufte, The Visual Display of Quantitative Information (London: Graphics Press, 1992)</ref> In early 1813 Napoleon raised a new army of 500,000 to replace his Russian losses. In the campaign of that year over 219,000 of Napoleon's soldiers were to die of typhus.<ref name=Typhus/> Typhus played a major factor in the Irish Potato Famine. During World War I, typhus epidemics killed over 150,000 in Serbia. There were about 25 million infections and 3 million deaths from epidemic typhus
in Russia from 1918 to 1922.<ref name=Typhus>

Smallpox

Smallpox is a highly contagious disease caused by the Variola virus. The disease killed an estimated 400,000 Europeans per year during the closing years of the 18th century.<ref>Smallpox and Vaccinia. National Center for Biotechnology Information.</ref> During the 20th century, it is estimated that smallpox was responsible for 300–500 million deaths.<ref>

</ref><ref>How Poxviruses Such As Smallpox Evade The Immune System, ScienceDaily, February 1, 2008</ref> As recently as early 1950s an estimated 50 million cases of smallpox occurred in the world each year.<ref>"Smallpox". WHO Factsheet. Retrieved on 2007-09-22.</ref> After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in December 1979. To this day, smallpox is the only human infectious disease to have been completely eradicated.<ref>

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Measles

Historically, measles was prevalent throughout the world, as it is highly contagious. According to the National Immunization Program, 90% of people were infected with measles by age 15. Before the vaccine was introduced in 1963, there were an estimated 3–4 million
cases in the U.S. each year.<ref name=autogenerated1>Center for Disease Control & National Immunization Program. Measles History, article online 2001. Available from http://www.cdc.gov.nip/diseases/measles/history.htm</ref> In roughly the last 150 years, measles has been estimated to have killed about 200 million people worldwide.<ref name=Measles/> In 2000 alone, measles killed some 777,000 worldwide.
There were some 40 million cases of measles globally that year.<ref>

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Measles is an endemic disease, meaning that it has been continually present in a community, and many people develop resistance. In populations that have not been exposed to measles, exposure to a new disease can be devastating. In 1529, a measles outbreak in Cuba killed two-thirds of the natives who had previously survived smallpox.<ref>Man and Microbes: Disease and Plagues in History and Modern Times; by Arno Karlen</ref> The disease had ravaged Mexico, Central America, and the Inca civilization.<ref>"Measles and Small Pox as an Allied Army of the Conquistadors of America" by Carlos Ruvalcaba, translated by Theresa M. Betz in “Encounters” (Double Issue No. 5-6, pp. 44–45)</ref>

Leprosy

Leprosy, also known as Wopat’s or Hansen's Disease, is caused by a bacillus, Mycobacterium leprae. It is a chronic disease with an incubation period of up to five years. Since 1985, 15 million people worldwide have been cured of leprosy.<ref>Leprosy 'could pose new threat'. BBC News. April 3, 2007.</ref> In 2002, 763,917 new cases were detected. It is estimated that there are between one and two million people permanently disabled because of leprosy.<ref>Leprosy (Hansen's Disease).Centers for Disease Control and Prevention (CDC).</ref>

Historically, leprosy has affected people since at least 600 BC, and was well recognized in the civilizations of ancient China, Egypt and India.<ref name=WHO_Factsheet>

</ref> During the High Middle Ages, Western Europe witnessed an unprecedented outbreak of leprosy.<ref>"Medieval leprosy reconsidered". International Social Science Review, Spring-Summer, 2006, by Timothy S. Miller, Rachel Smith-Savage.</ref><ref>

</ref> Numerous leprosaria, or leper hospitals, sprang up in the Middle Ages; Matthew Paris estimated that in the early 13th century there were 19,000 across Europe.<ref>

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Malaria

Malaria is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria.<ref>Malaria Facts. Centers for Disease Control and Prevention.</ref> Drug resistance poses a growing problem in the treatment of malaria in the 21st century, since resistance is now common against all classes of antimalarial drugs, except for the artemisinins.<ref>

</ref> The southern U.S. continued to be afflicted with millions of cases of malaria into the 1930s.<ref>Malaria. By Michael Finkel. National Geographic Magazine.</ref>

Yellow fever

Yellow fever has been a source of several devastating epidemics.<ref>Yellow Fever – LoveToKnow 1911.</ref> Cities as far north as New York, Philadelphia, and Boston were hit with epidemics. In 1793, one of the largest yellow fever epidemics in U.S. history killed as many as
5,000 people in Philadelphia—roughly 10% of the population.<ref>

Unknown causes

There are also a number of unknown diseases that were extremely serious but have now vanished, so the etiology of these diseases cannot be established. The cause of English Sweat in 16th-century England, which struck people down in an instant and was more greatly feared than even the bubonic plague, is still unknown.

Concern about possible future pandemics

Viral hemorrhagic fevers

Viruses causing viral hemorrhagic fever such as Lassa fever virus, Rift Valley fever, Marburg virus, Ebola virus and Bolivian hemorrhagic fever are highly contagious and deadly diseases, with the theoretical potential to become pandemics. Their ability to spread efficiently enough to cause a pandemic is limited, however, as transmission of these viruses requires close contact with the infected vector, and the vector only has a short time before death or serious illness. Furthermore, the short time between a vector becoming infectious and the onset of symptoms allows medical professionals to quickly quarantine vectors, and prevent them from carrying the pathogen elsewhere. Genetic mutations could occur, which could elevate their potential for causing widespread harm; thus close observation by contagious disease specialists is merited.

In the past 20 years, common bacteria including Staphylococcus aureus, Serratia marcescens and Enterococcus, have developed resistance to various antibiotics such as vancomycin, as well as whole classes of antibiotics, such as the aminoglycosides and cephalosporins. Antibiotic-resistant organisms have become an important cause of healthcare-associated (nosocomial) infections (HAI). In addition, infections caused by community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA) in otherwise healthy individuals have become more frequent in recent years. <!– Antibiotics are not described as “strongest”; each has a specific range of activity. Antibiotics that are effective against many types of bacteria are termed “broad spectrum”. Vancomycin is only effective against Gram-positive organisms, such as sensitive strains of S. aureus and Enterococcus. –> <!– HAIs are a serious concern, but do not meet the definition of a pandemic –>

Inappropriate antibiotic treatment and overuse of antibiotics have been an element in the emergence of resistant bacteria. The problem is further exacerbated by self-prescribing of antibiotics by individuals without the guidelines of a qualified clinician and the non-therapeutic use of antibiotics as growth promoters in agriculture.<ref name=Larson2007>

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SARS

In 2003, there were concerns that Severe Acute Respiratory Syndrome (SARS), a new and highly contagious form of atypical pneumonia, might become pandemic. It is caused by a coronavirus dubbed SARS-CoV. Rapid action by national and international health authorities such as the World Health Organization helped to slow transmission and eventually broke the chain of transmission, which ended the localized epidemics before they could become a pandemic. However, the disease has not been eradicated. It could re-emerge. This warrants monitoring and reporting of suspicious cases of atypical pneumonia.

Influenza

Wild aquatic birds are the natural hosts for a range of influenza A viruses. Occasionally, viruses are transmitted from these species to other species, and may then cause outbreaks in domestic poultry or, rarely, in humans.<ref name=sobrino6>

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H5N1 (Avian Flu)

In February 2004, avian influenza virus was detected in birds in Vietnam, increasing fears of the emergence of new variant strains. It is feared that if the avian influenza virus combines with a human influenza virus (in a bird or a human), the new subtype created could be both highly contagious and highly lethal in humans. Such a subtype could cause a global influenza pandemic, similar to the Spanish Flu, or the lower mortality pandemics such as the Asian Flu and the Hong Kong Flu.

From October 2004 to February 2005, some 3,700 test kits of the 1957 Asian Flu virus were accidentally spread around the world from a lab in the US.<ref>

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In May 2005, scientists urgently called upon nations to prepare for a global influenza pandemic that could strike as much as 20% of the world's population.<ref>

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In October 2005, cases of the avian flu (the deadly strain H5N1) were identified in Turkey. EU Health Commissioner Markos Kyprianou said: “We have received now confirmation that the virus found in Turkey is an avian flu H5N1 virus. There is a direct relationship with viruses found in Russia, Mongolia and China.” Cases of bird flu were also identified shortly thereafter in Romania, and then Greece. Possible cases of the virus have also been found in Croatia, Bulgaria and the United Kingdom.<ref>

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By November 2007, numerous confirmed cases of the H5N1 strain had been identified across Europe.<ref>

</ref> However, by the end of October only 59 people had died as a result of H5N1 which was atypical of previous influenza pandemics.

Avian flu cannot yet be categorized as a “pandemic”, because the virus cannot yet cause sustained and efficient human-to-human transmission. Cases so far are recognized to have been transmitted from bird to human, but as of December 2006 there have been very few (if any) cases of proven human-to-human transmission.<ref>WHO (2005). Avian Influenza A (H5N1) Infection in Humans http://www.nejm.org/doi/full/10.1056/NEJMra052211</ref> Regular influenza viruses establish infection by attaching to receptors in the throat and lungs, but the avian influenza virus can only attach to receptors located deep in the lungs of humans, requiring close, prolonged contact with infected patients, and thus limiting person-to-person transmission.

Biological warfare

In 1346, the bodies of Mongol warriors who had died of plague were thrown over the walls of the besieged Crimean city of Kaffa (now Theodosia). After a protracted siege, during which the Mongol army under Jani Beg was suffering the disease, they catapulted the infected corpses over the city walls to infect the inhabitants. It has been speculated that this operation may have been responsible for the arrival of the Black Death in Europe.<ref>

</ref> It is uncertain whether this documented British attempt successfully infected the Indians.<ref>Dixon, Never Come to Peace, 152–55; McConnell, A Country Between, 195–96; Dowd, War under Heaven, 190. For historians who believe the attempt at infection was successful, see Nester, Haughty Conquerors”, 112; Jennings, Empire of Fortune, 447–48.</ref>

During the Sino-Japanese War (1937–1945), Unit 731 of the Imperial Japanese Army conducted human experimentation on thousands, mostly Chinese. In military campaigns, the Japanese army used biological weapons on Chinese soldiers and civilians. Plague fleas, infected clothing, and infected supplies encased in bombs were dropped on various targets. The resulting cholera, anthrax, and plague were estimated to have killed around 400,000 Chinese civilians.<ref>

The Soviets suspected that two separate epidemics of hemorrhagic fever that swept the region in the late 1980s were caused by an accident in a lab where Chinese scientists were weaponizing viral diseases.<ref>William J Broad, Soviet Defector Says China Had Accident at a Germ Plant, New York Times, April 5, 1999</ref> In January 2009, an Al-Qaeda training camp in Algeria was reportedly wiped out by the plague, killing approximately 40 Islamic extremists. Some experts said that the group was developing biological weapons,<ref>Al-Qaeda cell killed by Black Death 'was developing biological weapons' Telegraph. January 20, 2009.</ref> however, a couple of days later the Algerian Health Ministry flatly denied this rumour stating “No case of plague of any type has been recorded in any region of
Algeria since 2003”.<ref>Plague outbreak denied Feb. 5, 2009.</ref>